The overall aim of this study is to demonstrate the feasibility to generate computerized human white matter tract maps based on a newly developed magnetic resonance imaging (MRI) technique, called diffusion tensor imaging (DTI). Knowledge of neuronal connections by the white matter tracts is of critical importance for the understanding of normal brain functions and abnormalities of function. However, to date most approaches have relied on invasive in vivo techniques and, necessarily, human data have been severely limited. In the DT] technique, the directionality (anisotropy) of water diffusion in the brain is measured. This technique provides two types of data that have previously been inaccessible. First, as we have demonstrated recently, it enables us reconstruct the 3-dimensional (3D) structure of white matter tracts. Second, it provides a unique contrast calli anisotropy map that indicates how anisotropic the water diffusion is and is believed to reflect the degree of fibe density and myelination. In this proposal, DTI measurements will be performed on postmortem tissues, which allow the acquisition o ultra high-resolution 3D DTI data. The long-term goals of this project are two-fold. First, these uniqui capabilities of the DTI technique provide novel opportunities to study neuroanatomy of human whiter matter and its variations due to individual, gender, normal and abnormal development/aging processes and other diseases. Second, the study will provide vital information for the future application of this novel technology to clinica studies, such as the range of normal deviation and nature and extent of expected white matter abnormalities in terms of DTI findings in each disease. Use of postmortem tissues also allows histology studies to explore the precise meanings of the DTI findings. To achieve these goals and as a Phase I feasibility study for Human Brain Project, this project is designed to build systems for data acquisition, fiber reconstruction, statistical analysis, am visualization. Toward this end, we propose five principal aims. 1) to acquire ultra high-resolution 3D DTI data of normal brains, 2) to develop fiber reconstruction technology, 3) to develop statistical tools to study individual variations in white matter structures, and 4) to develop tools to visualize 3D white matter architectures / creation of electric white matter atlas 3ERFORMANCE SITE(S) (organization, city, state) Department of Radiology, Johns Hopkins Medical Institute, Baltimore, MD 21205 KEY PERSONNEL. See instructions on Page 11. Use continuationpages as neededtoprovide the required information in the format shown below. Name Organization Role on Project SusumuMori, Ph.D.CL/ Dept.Radiology, Johns Hopkins Hospital PI Christos Davatzikos, Ph.D.C^ Dept.Radiology, Johns Hopkins Hospital Co-Inv. -Meiyappan Solaiyappan c\) Dept.Radiology, Johns Hopkins Hospital Co-Inv. Michail Miller, Ph.D. [unreadable]l/ Johns Hopkins University, Center of Imaging Science Co-Inv. Walter Kaufmann, M.D.Ci/ Dept. Pathology, Johns Hopkins Hospital Co-Inv. Barbara Grain, M.D. C^ Dept. Pathology, Johns Hopkins Hospital Co-Inv. Peter C.M. van Zijl, Ph.D.c/ Dept. Radiology, Johns Hopkins Hospital Consultant -Xu Dongrong, Ph.D. ex Dept. Radiology, Johns Hopkins Hospital Postdoc Jiangyang Zhang, Ph.D.c^/ Dept. Biomedical Engineering, Johns Hopkins Hospital Student PHS398(Rev. 5/95) 2 Principal Investigator/Program Director (Last, first, middle): SUSUHIU Mori Type the name of the principal investigator/program director at the top of each printed page and each continuation page. (For type specifications, see instructions on page 6.) RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page 1 Description,